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Ten children with transfusion dependent anemias (thalassemia, sideroblastic anemia, congenital pure red cell aplasia) received either intravenous desferrioxamine (DF) in increasing doses up to 450 mg/kg at the time of transfusion or daily subcutaneous DF up to 110 mg/kg on an outpatient basis. No patient on intravenous DF reached a negative iron balance. All children with a subcutaneous DF dose of more than 60 mg/kg obtained a negative iron balance with a net iron excretion (transfusion iron already substracted) between 206 to 810 mg (mean 496 mg) monthly. The effectiveness of regular subcutaneous DF on liver storage iron could be confirmed in 4 patients by liver biopsy, showing a decrease between 40–60% iron after 12–14 months of chelation therapy. So far the daily iron excretion has remained constant with a given dose of DF over a period up to 15 months. Even if poor compliance in some patients is taken into account, it is possible with this method of treatment to prevent further accumulation of iron in chronically transfused children.

Oxygen equilibrium curves of partially autoxidized adult (HbA) and fetal hemoglobins (HbF) were determined at 2–75 methemoglobin (met-Hb). Hemoglobin concentration of 5 mM, pH 7.15 (Tris 0.05 M), and temperature of 37° corresponded to intraerythrocytic in vivo conditions. With increasing met-Hb fractions the curves became shifted to the left and approached a hyperbolic form: P50of both HbA and HbF decreased in absence of 2, 3-diphosphoglycerate (2, 3-DPG) from about 13 to 7 Torr, and Hill's n from 2.7 to 1.25. Independent of the met-Hb fraction the alkaline Bohr effect was increased by 2, 3-DPG. The allosteric effect of 2, 3-DPG on P50decreased with increasing met-Hb. At all oxidation levels this effect was smaller on HbF than on HbA: At 50 met-Hb P50of HbF is increased by 0.7 Torr/mM 2, 3-DPG increase, P50of HbA by 1.3 Torr, respectively. There was no evidence of preferential autoxidation of α or non-α chains of the hemoglobin molecule.

Blood volume was studied in 160 infants and children aged from one hour to 14 years. From these data linear and logarithmic regression equations relating blood volume to weight, height and surface area were calculated. Equations utilizing combined height and logarithmic weight values were found to be the most accurate for predicting blood volume. Therefore, nomograms were constructed for reading blood volume directly from height and weight.

Venous and capillary hematocrit, acid base values, and circulatory parameters were measured simultaneously in 92 newborn infants within six hours of birth. Gestational age ranged from 26 to 41 weeks. The capillary/ venous hematocrit ratio (Hctc/Hctv) was greater than 1.00 in 89 infants. We found significant inverse correlations between Hctc/Hctv and several parameters, such as pH (r=-0.82), standard bicarbonate (r=-0.73), systolic blood pressure (r=-0.51), and peripheral blood flow (r=-0.70). Most of the infants with a Hctc/Hctv of 1.20 and above had red cell mass values of less than 35 ml/kg. However, blood volume apparently did not influence the Hctc/Hctv. Gestational age appeared to affect Hctc/Hctv only before 30 weeks, when compared with the Hctc/Hctv of term infants. Our results indicate that disturbed circulation, and in particular, disturbed microcirculation, is involved in the development of high Hctc/Hctv ratios. We strongly advise that hematocrits obtained by skin prick from a sick newborn infant should not be relied on as they may give misleading information on oxygen carrying capacity to vital organs.

Blood volume and its components were estimated using 125iodinated human serum albumin in 194 newborn infants with 26 to 41 week gestations. Umbilical cords were ligated 15 seconds after vaginal delivery (n=141) and within 5 seconds after delivery by Caesarean section (n=53). The infants were divided into four groups according to the mode of delivery and presence of prenatal complications: group I: vaginal deliveries (n=96) and group II: Caesarean section (n=25) without preceding complications; group III: infants with intra-uterine asphyxia (n=56); group IV: infants with tight umbilical cord loops around neck (n=17). Subgroups were established with respect to gestational age and to one-minute Apgar scores. Significantly different blood volume (BV) and red cell mass (RCM) values between the subgroups were only found in group I with respect to different Apgar scores: Ia Apgar>5: BV 77.9±6.2; RCM 37.5±5.1 ml/kg; Ib Apgar<6: BV 70.0±4.4; RCM 29.6±2.9 ml/kg (P<0.005). Intra-partum asphyxia did not affect BV (71.3±4.8 ml/kg) and RCM (31.2±3.6 ml/kg) in group II. BV and RCM were significantly (P<0.005) lower than in group Ia. In group III, BV (90.4±7.0 ml/kg) and RCM (46.9±6.3 ml/kg) were significantly (P<0.005) higher than in group I, irrespective of the mode of delivery and Apgar scores. The infants of group IV had the lowest volumes (BV 67.5±5.7; RCM 27.4±2.7 ml/kg). Values obtained in premature and full-term infants were similar in the respective groups. These results indicate that infants with intra-partum asphyxia and with tight nuchal cords do not participate in placental transfusion or even lose some blood into the placenta. However, infants with intrauterine asphyxia (excepting those with tight nuchal cords) receive marked placental transfusion in utero.

Red cell mass (RCM) was estimated using 125I-labelled human serum albumin in 128 premature infants born after 26 to 36 weeks gestation. Infants of three different gestational periods (26–29, 30–32, and 33–36 weeks) with respiratory distress (RD) averaged lower one-minute Apgar scores and lower RCM than infants without RD (P<0.05). The incidence of RD was significantly (P<0.05) higher in infants with Apgar scores below 6 and in infants with RCM of less than 35 ml/kg than in the infants with greater values. The highest incidence of RD and the highest mortality rate were found in the infants with low Apgar scores and low RCM values. Prematures with similar Apgar scores showed a higher incidence of RD when RCM was low, and infants with similar RCM showed a higher incidence of RD when Apgar scores were low. Our results suggest that both birth asphyxia and deficiency of red cell mass interfere with postnatal cardio-respiratory adaptation. In high-risk premature infants, erythrocytes should be transfused when the venous haematocrit is below 0.45.

Peripheral blood flow and systolic blood pressure (strain-gauge plethysmograph), blood volume (Evans blue) and whole blood viscosity (cone-plate viscometer) have been measured in 66 premature and full-term infants 6 to 144h of age. Blood flow and blood volume were moderately decreased in the infants with respiratory distress. Highly significant (P<0.001) correlations were found betwen blood flow and blood volume (r=0.77), blood pressure and blood volume (r=0.50), peripheral resistance and blood volume (r=-0.44), blood flow and blood pressure (r=0.50), blood flow and peripheral resistance (r=-0.67), peripheral resistance and blood viscosity (r=0.45), and blood viscosity and haematocrit (r=0.86). There was no correlation between peripheral blood flow and blood viscosity. However, at given blood volume, peripheral blood flow decreased with increasing blood viscosity. These results indicate that in newborn infants peripheral blood flow, blood pressure and peripheral resistance are influenced by blood volume, but also depend on blood viscosity.

A sample of 38 clinically unaffected carriers for various lipidoses and their noncarrier relatives was studied with biochemical, psychological, and neuropsychological tests under blind conditions. The largest group of carriers was that for metachromatic leucodystrophy (MLD). The mean activity of arylsulphatase A or cerebroside sulphatase in the obligate carriers was 25%–30% of the control values, some heterozygotes showing little more activity than MLD patients. It was found that compared with the controls all heterozygotes (both obligate and facultative) differ unfavourably in some personality traits and in WISA subtests, including capacity for spatial cognition. These differences are especially obvious in a group of seven MLD carriers from the same family.

Detection of a patient suffering from Krabbe's disease led to carrier screening in his family. Determination of galactosylceramide ß-galactosidase activity revealed the occurrence of two different alleles among the carriers of the same family. Heterozygotes and their noncarrier relatives were studied using psychometric and neuropsychological tests under blind conditions. It was found that compared to seven adult noncarrier relatives 19 adult carriers differ significantly in their general IQ and some subtests of the Wechsler Intelligence Scale for adults (WISA), including spatial cognition. Reaction times were significantly slower in the carriers with enzyme activity below 25% of the control values. Most of the carriers of this family have had myopia since early childhood.

Zusammenfassung Tierexperimentelle Befunde ergaben den Hinweis, daß bei Knochenmarktransplantation mit inkompatiblem Spendermark eine Vorinkubation des Spendermarkes mit xenogenem Anti-T-Zell-Globulin eine sonst toxisch verlaufende Graft versus Host-(GvH)Erkrankung vermeidet. Bei drei Patienten mit akuter lymphatischer Leukämie wurde dieses Prinzip bei der Knochenmarktransplantation erfolgreich klinisch angewandt. Zur Anwendung gelangte ein spezifisches antihumanes Anti-T-Zell-Globulin (ATCG-H), das durch mehrere Absorptionsschritte aus rohem antihumanem Globulin (ATG) gewonnen wurde. Eine Vortestung des Serums ergab eine unveränderte Reaktion gegen menschliche T-Zell-Lymphozyten ohne toxische Nebenwirkungen auf in vitro nachweisbare Vorläuferzellen der Hämopoese (CFU-C).

Summary: Oxygen equilibrium curves of partially autoxidized adult (HbA) and fetal hemoglobins (HbF) were determined at 2–75% methemoglobin (met-Hb). Hemoglobin concentration of 5 mM, pH 7.15 (Tris 0.05 M), and temperature of 37° corresponded to intraerythrocytic in vivo conditions. With increasing met-Hb fractions the curves became shifted to the left and approached a hyperbolic form: P50of both HbA and HbF decreased in absence of 2, 3-diphosphoglycerate (2, 3-DPG) from about 13 to 7 Torr, and Hill's n from 2.7 to 1.25. Independent of the met-Hb fraction the alkaline Bohr effect was increased by 2, 3-DPG. The allosteric effect of 2, 3-DPG on P50decreased with increasing met-Hb. At all oxidation levels this effect was smaller on HbF than on HbA: At 50% met-Hb P50of HbF is increased by 0.7 Torr/mM 2, 3-DPG increase, P50of HbA by 1.3 Torr, respectively. There was no evidence of preferential autoxidation of a or non-a chains of the hemoglobin molecule.Oxidized hemoglobin does not take part in oxygen transport. In addition a left-shifted, more hyperbolic curve means restricted oxygen unloading from the remaining active hemoglobin. Thus, from application of our results to clinical conditions it must be concluded that sustained methemoglobinemia, despite partial compensation by 2, 3-DPG, may interfere with oxygen supply to tissue, particularly in the perinatal period, when HbF prevails.Speculation: Tissue oxygen supply, as calculated from the present data on O2capacity, P50, 2, 3-DPG reactivity, Hill's n, and Bohr factors, appears to be markedly lowered in methemoglobinemia, particularly in presence of fetal hemoglobin. Reduced tissue oxygen supply in the perinatal period, in addition to a generalized cytochrome b5reductase deficiency (22), might contribute to irreversable cerebral dysfunction in hereditary methemoglobinemia.

Zusammenfassung In einer norddeutschen Familie, die cyanotische Individuen in 3 Generationen aufweist, wurde HbM als Ursache der Cyanose festgestellt. Ein Kind konnte von Geburt an beobachtet werden; es entwickelte erst im Ablauf einiger Wochen die charakteristische Cyanose. Daraus war abzuleiten, daß die Anomalie in derß-Kette des Hämoglobins liegen mußte. Dies ließ sich im Hybridisierungsexperiment mit Hundehämoglobin als zutreffend erweisen. Die Untersuchung der Peptide der durch Gegenstromverteilung aus Globin isoliertenß-Kette mittels „fingerprint“ ergab ein anomales PeptidßT7. Die quantitative Aminosäureanalyse dieses Peptids zeigte, daß darin Histidin fehlte, dagegen Tyrosin vorhanden war, woraus folgt, daß in Position 63 derß-Kette ein Histidin-Tyrosin-Austausch vorliegt. Das entspricht den Verhältnissen in HbM Saskatoon.

Zusammenfassung Durch Zentrifugieren oder fraktionierte osmotische Hämolyse wurden von menschlichen Erythrozyten Fraktionen mit einer Anreicherung von jungen und alten Zellen gewonnen.

Zusammenfassung Durch Behandlung alkoholfixierter Blutausstriche mit Zitronensäure-Phosphatpuffer (pH 3.4) bei 37° gelingt es, den Blutfarbstoff aus Erwachsenen-erythrozyten völlig zu extrahieren, während er unter den gleichen Bedingungen aus der Hauptmenge der Erythrozyten Neugeborener nicht herausgelöst wird. Im Modellversuch mit Hb-getränkten Filtrierpapierstreifen wird belegt, daß die differente Extrahierbarkeit von den Hämoglobinen Hb A und Hb F selbst abhängt.

In-vitro oxygen dissociation curves were constructed for 14 subjects. To uncover individual variations, at least 3 curves were drawn for most subjects over a period of several weeks. In 5 subjects they were drawn over a period of 2 years. The resultant individual characteristics are constant for years. The maximum variation of oxygen partial pressure necessary to produce 50% saturation in our subjects amounted to 5.4 mm Hg. The mean partial pressure of oxygen for half saturation from all experiments was 26.8 mm Hg, standard deviation ±2.6. A new „Standard Oxygen Dissociation Curve“ is presented.

Structural characterization of a new variant of human hemoglobin (adult), designated hemoglobin Freiburg, indicates the deletion of the valyl residue No. 23 from an otherwise normal beta-chain. The formula may be written α2β223val—0. The abnormal hemoglobin is present with hemoglobin A in the proposita and in two of her three living children, but is not detectable in her parents. We postulate that this variant represents a triplet base deletion which most likely resulted from an unequal crossing-over between two normal beta-chain loci during meiosis in one of the parents of the proposita.

Zusammenfassung Elektrophoretische Blutfarbstoffuntersuchungen haben in Deutschland nur dann einen Sinn, wenn sie zur Differentialdiagnose der heterozygoten Thalassämie (Thalassaemia minor und minima) brauchbar sind. Hierzu ist die quantitative Bestimmung der „langsamen Fraktion“ Hb A2 des Blutfarbstoffs erforderlich. Sie läßt sich mit genügender Genauigkeit nur mit der Stärkeblockelektrophorese durchführen. Anomale Varianten des Blutfarbstoffs, für deren Untersuchung die Papierelektrophorese ausreicht, wurden in Deutschland bisher noch nicht beobachtet; nicht allzu selten kommt jedoch die Thalassämie im deutschen Sprachgebiet vor.

Zusammenfassung Ein 3 Jahre alter Junge erkrankte an einer durch ein Coxsackie-A-Virus bedingten Herpangina, der 10 Tage nach Erkrankungsbeginn eine schwere akute hämolytische Anämie vom TypLederer-Brill nachfolgte. Als charakteristische hämatologische Befunde werden Mikrosphärocytose, herabgesetzte osmotische Resistenz und Erythrophagocytose im peripheren Blut und im Knochenmark festgestellt. In Serum und Harn zeigte die spektrophotometrische Analyse Oxyhämoglobin, sowie einen Körper von der Art eines an Eiweiß gebundenen Hämatins. Die Cholesterinwerte waren stark erhöht.